BAP1 loss is unusual in well-differentiated papillary mesothelioma and may predict development of malignant mesothelioma

Our plain-English summary of BAP1 loss is unusual in well-differentiated papillary mesothelioma and may predict development of malignant mesothelioma, by H.E. Lee, J.R. Molina, W.R. Sukov, et al (Human Pathology, 2018).

The study

• Authors: H.E. Lee, J.R. Molina, W.R. Sukov, A.C. Roden, E.S. Yi
• Journal: Human Pathology
• Published: 2018;79:168-176
• Type of article: Case report
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Literature on BRCA1-associated protein 1 (BAP1) expression status in well-differentiated papillary mesothelioma (WDPM) is limited. In the present study, we examined the prevalence of BAP1 loss in WDPM by immunohistochemistry with clinical correlation, along with CDKN2A deletion status by fluorescence in situ hybridization (FISH). Eight patients diagnosed as having WDPM were identified from the surgical pathology file. Adenomatoid tumors (n = 8) and malignant mesothelioma (MM) (n = 39) were included for comparison. BAP1 immunohistochemistry was performed on representative block(s) from each case. CDKN2A FISH was also performed in the WDPMs and adenomatoid tumors. Clinical information was obtained from the medical records. Three of 8 WDPM patients showed synchronous or metachronous MM. All 3 cases showed BAP1 loss in both WDPM and the matched MM. Single-nucleotide polymorphism genomic microarray (n = 3) demonstrated a similar genetic profile in the WDPM and MM components, which supports their clonal relationship. The remaining 5 WDPM cases had intact BAP1 expression and had no evidence of disease on follow-up imaging studies at 1 to 71 months (median, 35 months). All 8 adenomatoid tumors had intact BAP1 expression, whereas 17 of 39 MM had BAP1 loss. CDKN2A FISH was negative for deletion in 4 WDPMs tested (including the case that developed MM) and all 8 adenomatoid tumors. In our study, WDPM did not show CDKN2A deletion in any case. BAP1 loss was also absent in all pure WDPM cases but was identified in all WDPM with synchronous or metachronous MM. Similar genetic landscape in WDPM and MM components suggested their clonal relationship.

Copyright © 2018 Elsevier Inc. All rights reserved.

In plain English

This study, from the Mayo Clinic in Rochester, looked at well-differentiated papillary mesothelioma (WDPM), a rare tumor of the lining of body cavities, in 8 patients diagnosed between 2004 and 2016. The authors tested the tumors for loss of a protein called BAP1, and some for deletion of the CDKN2A gene. For comparison they also tested 8 adenomatoid tumors and 39 malignant mesotheliomas. Three of the 8 WDPM patients also had malignant mesothelioma, either at the same time or, in one woman, about 10 years later. All 3 showed BAP1 loss in both tumors. The 5 patients with WDPM alone kept BAP1. BAP1 was lost in 17 of 39 malignant mesotheliomas and in none of the adenomatoid tumors. No CDKN2A deletion was found in the WDPMs tested. Genetic testing found shared abnormalities between the paired tumors in 2 of the 3 patients. Two WDPM patients had a history of asbestos exposure, 3 had none, and 3 were unknown. The authors concluded that BAP1 loss in WDPM may be associated with later malignant mesothelioma, and said more studies were needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective case series of WDPM cases from a surgical pathology file, with adenomatoid tumors and malignant mesotheliomas as comparison (control) cases; laboratory tests were BAP1 immunohistochemistry, CDKN2A FISH and SNP genomic microarray
• Who was studied: 8 patients with WDPM (4 men, 4 women, aged 25 to 70) identified at Mayo Clinic Rochester for 2004 to 2016; controls were 8 adenomatoid tumors and 39 malignant mesotheliomas (34 pleural, 2 pericardial, 2 peritoneal)
• Exposure: The study examined BAP1 protein loss and CDKN2A gene deletion in tumors, not asbestos. Asbestos history was recorded: 2 WDPM patients had exposure (one with extensive exposure, who also had malignant mesothelioma), 3 had none (including 2 who had malignant mesothelioma), and 3 were unknown. No fiber types or doses were given.
• Main results:
  • The 5 WDPMs without malignant mesothelioma kept BAP1 expression.
  • All 3 WDPM patients who had malignant mesothelioma at the same time or later showed BAP1 loss.
  • In one patient, a WDPM with BAP1 loss was followed by widespread malignant mesothelioma 10 years after the first diagnosis.
  • Comparison groups: all 8 adenomatoid tumors kept BAP1, while 17 (43.6%) of 39 malignant mesotheliomas had BAP1 loss.
  • CDKN2A FISH showed a normal pattern (no deletion) in the 4 WDPMs tested, and all 8 adenomatoid tumors were negative for deletion.
  • In two of the three patients with both tumors, genomic microarray found shared genetic abnormalities between the WDPM and the malignant mesothelioma. The third patient showed a normal pattern in both.
  • One patient with WDPM alone had no disease progression at 2 months after surgery and was then lost to follow-up.
• The authors' conclusion: The authors concluded that BAP1 loss in WDPM may be associated with later development of malignant mesothelioma. They wrote that it would indicate an unfavorable prognosis and should prompt clinicians to look further for malignant mesothelioma.
• Limitations the authors state:
  • The authors said more studies are needed to confirm their observation.
  • The authors acknowledged that the tumor first diagnosed as WDPM in the 10-year case might have been malignant mesothelioma from the start, although they argued against this.
  • In one of the three paired cases, the normal genetic profile did not directly support a relationship between the WDPM and the malignant mesothelioma.
  • One WDPM case did not have enough tissue left for CDKN2A FISH.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: BAP1, Well-Differentiated Papillary Mesothelioma, Malignant Mesothelioma, Immunohistochemistry, CDKN2A, Fluorescence In Situ Hybridization (FISH), Pathology, Adenomatoid Tumor.

Related studies

• Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma — R. Pillappa, J.J. Maleszewski, et al. (2018)
• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)
• Loss of expression of BAP1 predicts longer survival in mesothelioma — M. Farzin, C.W. Toon, et al. (2015)
• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)
• Well-differentiated papillary mesothelioma: clustering in a Portuguese family with a germline BAP1 mutation — C. Ribeiro, S. Campelos, et al. (2013)

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